Characteristics and anticancer properties of Sunitinib malate-loaded poly-lactic-co-glycolic acid nanoparticles against human colon cancer HT-29 cells lines

Purpose: To develop poly-lactic-co-glycolic acid (PLGA) -based nanoparticles (NPs) for the delivery of sunitinib malate (STM) to colon cancer cells.Methods: Three different formulations (F1 – F3) were developed by nano-precipitation technique using various concentrations of PLGA. The NPs were evaluated for particle size, polydispersity index, zeta potential, drug entrapment, and drug loading, using differential scanning calorimetry (DSC), Fouriertransform infrared spectroscopy (FTIR), x-ray diffraction (XRD), and scanning electron microscopy (SEM). Furthermore, in vitro drug release and anticancer studies were carried out on the formulations.Results: Among the three NPs, optimized NP (F3) of STM was chosen for in vitro anti-cancer study against H-29 human colon cancer cells lines based on its particle size (132.9 nm), PDI (0.115), zeta potential (-38.12 mV), entrapment efficiency (52.42 %), drug loading (5.24 %), and drug release (91.26 % in 48 h). A significant anti-cancer activity of the optimized NPs was observed, relative to free STM.Conclusion: These findings suggest that STM-loaded NPs possess significant anti-cancer activity against human colon cancer HT-29 cells lines.Keywords: Sunitinib malate, Poly-lactic-co-glycolic acid, Nanoparticles, Colon cance

TEMPERATURE DEPENDENT SOLUBILITY STUDIES OF BRIGATINIB IN SOME PURE SOLVENTS USEFUL IN DOSAGE FORM DEVELOPMENT

In the current study, thermodynamic dissolution of brigatinib in six pure solvents namely, water, ethanol, isopropyl myristate (IPM), poly(ethylene glycol)-400 (PEG-400), dichloromethane (DCM) and ethyl acetate (EA) at (298.2-323.2K) temperature and 0.1 MPa atm. pressure were carried out using flask shaking technique.The mole-fraction solubility of brigatinib was obtainedgreatest in IPM (6.09 x 10-2) and least in water (3.12 x 10-6) at298.2 K.Experimentally obtained solubilities values of brigatinib were regressed using adapted Apelblat equation with root mean square deviations in the range of 1.91 to 4.67 in all solvents and similar trends were observed with increased the temperature. The solubility data generated in this investigation could be helpful for investigator for analysis/dosage form development of brigatinib

Exploitation of Design-of-Experiment Approach for Design and Optimization of Fast-Disintegrating Tablets for Sublingual Delivery of Sildenafil Citrate with Enhanced Bioavailability Using Fluid-Bed Granulation Technique

Sildenafil citrate undergoes first-pass metabolism, resulting in poor oral bioavailability at 25–41% of the administered dose. This study aimed to design and optimize fast-disintegrating tablets for the sublingual delivery of sildenafil citrate to improve bioavailability and facilitate rapid onset of action. The design-of-experiment (DoE) approach using 32 full factorial design was conducted to develop a new formulation of sildenafil fast-disintegrating sublingual tablets (FDSTs) using the fluid-bed granulation technique. The levels of partially pre-gelatinized starch (5–15%) and microcrystalline cellulose (10–60%) were selected as independent formulation variables. The prepared FDSTs were investigated for physical properties. Further, the optimum formulation was chosen for in vivo study in rabbits. Regression analysis showed that independent variables have a significant (p < 0.05) influence on critical attributes of FDSTs. The optimized formulation showed acceptable mechanical strength (friability < 1.0%) with very fast disintegration (14.561 ± 0.84 s) and dissolution (94.734 ± 2.76% after 15 min). Further, the optimized formulation demonstrated a significant increase (p < 0.01) in Cmax and AUC0–∞ with short tmax compared to the market product (Viagra®). Based on these results, using the DoE approach, a high level of assurance was achieved for FDSTs’ product quality and performance

Nanotechnology in Cosmetics and Cosmeceuticals—A Review of Latest Advancements

Nanotechnology has the potential to generate advancements and innovations in formulations and delivery systems. This fast-developing technology has been widely exploited for diagnostic and therapeutic purposes. Today, cosmetic formulations incorporating nanotechnology are a relatively new yet very promising and highly researched area. The application of nanotechnology in cosmetics has been shown to overcome the drawbacks associated with traditional cosmetics and also to add more useful features to a formulation. Nanocosmetics and nanocosmeceuticals have been extensively explored for skin, hair, nails, lips, and teeth, and the inclusion of nanomaterials has been found to improve product efficacy and consumer satisfaction. This is leading to the replacement of many traditional cosmeceuticals with nanocosmeceuticals. However, nanotoxicological studies on nanocosmeceuticals have raised concerns in terms of health hazards due to their potential skin penetration, resulting in toxic effects. This review summarizes various nanotechnology-based approaches being utilized in the delivery of cosmetics as well as cosmeceutical products, along with relevant patents. It outlines their benefits, as well as potential health and environmental risks. Further, it highlights the regulatory status of cosmeceuticals and analyzes the different regulatory guidelines in India, Europe, and the USA and discusses the different guidelines and recommendations issued by various regulatory authorities. Finally, this article seeks to provide an overview of nanocosmetics and nanocosmeceuticals and their applications in cosmetic industries, which may help consumers and regulators to gain awareness about the benefits as well as the toxicity related to the continuous and long-term uses of these products, thus encouraging their judicious use

Efficacy of SPG-ODN 1826 Nanovehicles in Inducing M1 Phenotype through TLR-9 Activation in Murine Alveolar J774A.1 Cells: Plausible Nano-Immunotherapy for Lung Carcinoma

Alveolar macrophages are the first line of defense against intruding pathogens and play a critical role in cancer immunology. The Toll-like receptor (TLR) family mediates an important role in recognizing and mounting an immune response against intruding microbes. TLR-9 is a member of the intracellular TLR family, which recognizes unmethylated CG motifs from the prokaryotic genome. Upon its activation, TLR-9 triggers downstream of the MyD-88-dependent transcriptional activation of NF-κB, and subsequently results in abundant inflammatory cytokines expression that induces a profound inflammatory milieu. The present exploratory investigation aimed at elucidating the potency of schizophyllan for entrapping ODN 1826 (SPG-ODN 1826)-mediated stimulation of TLR-9 in provoking an inflammatory-type response in murine alveolar macrophages. Schizophyllan (SPG), a representative of the β-glucan family, was used in the present study as a nanovehicle for endosomal trafficking of CpG ODN 1826. TEM analysis of SPG-ODN 1826 nanovehicles revealed that the prepared nanovehicles are spherical and have an average size of about 100 nm. Interestingly, SPG-ODN 1826 nanovehicles were competent in delivering their therapeutic payload within endosomes of murine alveolar macrophage (J774A.1) cells. Exposure of these nanovehicles within LPS stimulated J774A.1, resulted in a significant provocation of reactive oxygen species (ROS) (p < 0.01) in comparison to CpG ODN 1826 alone. Moreover, the formulated nanovehicles succeeded in generating a profound Th1-based cytokine profile constituted by enhanced expression of IFN-γ (p < 0.001) and IL-1β (p < 0.001) inflammatory cytokines. These findings clearly indicated the immunostimulatory potential of SPG-ODN 1826 nanovehicles for inducing the Th1-type phenotype, which would certainly assist in skewing M2 phenotype into the much-desired M1 type during lung cancer

Application of hydrophilic polymers for the preparation of tadalafil solid dispersions: micromeritics properties, release and erectile dysfunction studies in male rats

The objective of the present study was to improve the dissolution rate and aphrodisiac activity of tadalafil by using hydrophilic polymers. Solid dispersions were prepared by solvent evaporation-Rota evaporator using Koliphore 188, Kollidon® VA64, and Kollidon® 30 polymers in a 1:1 ratio. Prepared tadalafil-solid dispersions (SDs) evaluated for yield, drug content, micromeritics properties, physicochemical characterizations, and aphrodisiac activity assessment. The optimized SDs TK188 showed size (2.175 ± 0.24 µm), percentage of content (98.89 ± 1.23%), yield (87.27 ± 3.13%), bulk density (0.496 ± 0.005 g/cm3), true density (0.646 ± 0.003 g/cm3), Carr’s index (23.25 ± 0.81), Hausner ratio (1.303 ± 0.003) and angle of repose (<25°). FTIR spectrums revealed tadalafil doesn’t chemically interact with used polymers. XRD and DSC analysis represents TK188 SDs were in the amorphous state. Drug release was 97.17 ± 2.43% for TK188, whereas it was 32.76 ± 2.65% for pure drug at the end of 2 h with 2.96-fold increase in dissolution and followed release kinetics of Korsmeyer Peppa’s model. MDT and DE were noted to be 17.48 minutes and 84.53%, respectively. Furthermore, TK188 SDs showed relative improvement in the sexual behavior of the male rats. Thus the developed SDs TK188 could be potential tadalafil carriers for the treatment of erectile dysfunction

Preparation and Characterization of a Novel Mucoadhesive Carvedilol Nanosponge: A Promising Platform for Buccal Anti-Hypertensive Delivery

Carvedilol (CRV) is a non-selective third generation beta-blocker used to treat hypertension, congestive heart failure and angina pectoris. Oral administration of CRV showed poor bioavailability (25%), which might be ascribed to its extensive first-pass metabolism. Buccal delivery is known to boost drugs bioavailability. The aim of this study is to investigate the efficacy of bilosomes-based mucoadhesive carvedilol nanosponge for enhancing the oral bioavailability of CRV. The bilosomes were prepared, optimized and characterized for particle size, surface morphology, encapsulation efficiency and ex-vivo permeation studies. Then, the optimized formula was incorporated into a carboxymethyl cellulose/hydroxypropyl cellulose (CMC/HPC) composite mixture to obtain buccal nanosponge enriched with CRV bilosomes. The optimized bilosome formula (BLS9), showing minimum vesicle size, maximum entrapment, and highest cumulative in vitro release, exhibited a spherical shape with 217.2 nm in diameter, 87.13% entrapment efficiency, and sustained drug release for up to 24 h. In addition, ex-vivo drug permeation across sheep buccal mucosa revealed enhanced drug permeation with bilosomal formulations, compared to aqueous drug suspension. Consecutively, BLS9 was incorporated in a CMC/HPC gel and lyophilized for 24 h to obtain bilosomal nanosponge to enhance CRV buccal delivery. Morphological analysis of the prepared nanosponge revealed improved swelling with a porosity of 67.58%. The in vivo assessment of rats indicated that CRV-loaded nanosponge efficiently enhanced systolic/diastolic blood pressure, decreased elevated oxidative stress, improved lipid profile and exhibited a potent cardio-protective effect. Collectively, bilosomal nanosponge might represent a plausible nanovehicle for buccal delivery of CRV for effective management of hypertension

COVID 19 pandemic challenges and their management: A review of medicines, vaccines, patents and clinical trials with emphasis on psychological health issues

The SARS‐CoV‐2 (COVID 19) paroxysm is a dominant health exigency that caused significant distress, affecting physical and mental health. Increased mortality, a stressed healthcare system, financial crisis, isolation, and new living and working styles enhanced societal commiseration leading to poor health outcomes. Though people try to maintain good physical health but unfortunately the mental affliction is still ignored. Poor psychological health has emerged as a burgeoning social issue and demands attention. Henceforth, the fundamental objective of this review article is to collate information about COVID-linked physical and psychological agony in diverse population groups with related symptoms and accessible diagnosis techniques. Recent studies have unraveled the fragile mental states of people who have either contracted COVID 19 or had near and dear ones falling prey to it. The impact of the epidemic on the human mind both in short and long-term, with possible risk and preventive factors together with suggested solutions for maintaining good health have also been discussed here. It also enlists the available medications, vaccines and investigational research in the form of patents and clinical trials. This article can be taken as an updated information sheet for COVID 19, accompanied by its management techniques with special emphasis on coping strategies for mental health. Further, it may also assist the policymakers to devise approaches that could enable the public to overcome the pandemic-driven adversity not only in the given situation but also futuristically